Urinary incontinence (UI) is a major problem for older women, causing significant psychological and medical morbidity and engendering a $15 billion annual cost that exceeds the entire NIH budget. The most common type of UI in older women is urge UI, which is generally associated with involuntary bladder contractions-a condition known as detrusor overactivity (DO). Yet little is known about the pathogenesis and interrelationship of urge UI and DO in older women. Moreover, it remains unclear how, how well, and in which older women drug therapy works, and whether patients themselves consider the improvement significant. Based on our pilot data, we postulate that there is a bimodal response, with many women experiencing significant improvement while an equal proportion worsen. In addition, these data suggest for the first time that clinical and physiological variables may predict outcome, and, significantly, provide insights into the mechanisms of improvement. The specific aims of the proposed study are to: 1) identify which traditional as well as newer physiological parameters predict treatment outcome in community-dwelling older women (controlling for placebo response); and 2) identify which parameters mediate both drug and placebo responses. To accomplish these goals we will enroll 250 community-dwelling older women with urge UI in a randomized controlled trial of oxybutynin. Outcome measures will include changes in incontinence frequency, urodynamic parameters, and subjective response. In addition, to determine the smooth muscle physiological correlates of response, we will blindly examine biopsies of detrusor smooth muscle obtained from a sample of women who do and do not respond to oxybutynin. By evaluating newer physiological tests, identifying likely outcome predictors, and providing insights into the mechanism(s) that underlie treatment response, the proposed study should provide novel and crucial insights to advance understanding of the pathophysiology of the most common form of UI in older women, thereby facilitating development of newer therapeutic options that are desperately needed.